Publications by authors named "Hyoung Doo Shin"

296 Publications

Association of APOE genotype with lipid profiles and type 2 diabetes mellitus in a Korean population.

Genes Genomics 2021 Apr 17. Epub 2021 Apr 17.

Department of Life Science, Sogang University, Seoul, 04107, Republic of Korea.

Background: Type 2 diabetes mellitus (T2DM) is associated with chronic hyperglycemia and lipid metabolism. A previous genome-wide association study revealed the TOMM40-APOE region as novel locus for T2DM susceptibility.

Objective: This association study was conducted to determine the genetic effects of APOE single nucleotide polymorphisms (SNPs) on T2DM susceptibility and lipid profiles in a Korean population.

Methods: A total of 6 tagging SNPs, including rs7412 and rs429358, were selected for ε genotype analysis and genotyped in 1436 subjects, consisting of 352 T2DM patients and 1084 unaffected controls.

Results: Logistic regression analyses were conducted and there were no significant associations among the APOE 6 tagging SNPs, ε genotypes, and haplotypes with T2DM susceptibility. To investigate the association of the APOE tagging SNPs with the lipid profiles, a regression analysis was conducted. As a result, rs7412 was significantly associated with the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels (P = 2.30 × 10 and 3.39 × 10, respectively) in the unaffected controls. The ε2 allele and ε3 allele were significantly associated with the TC (P = 4.46 × 10 and 0.02, respectively) and LDL levels (P = 3.54 × 10 and 0.0006, respectively) in the unaffected controls. Further analysis of only the unaffected controls was conducted. As a result, the APOE alleles ε2 and ε3 showed a significant association with the TC and LDL levels (P < 0.05).

Conclusion: The results of this study may help in understanding APOE polymorphisms and ε alleles and lipid profiles, which have been highly linked to T2DM, in a Korean population.
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http://dx.doi.org/10.1007/s13258-021-01095-yDOI Listing
April 2021

A non-synonymous variant rs12614 of complement factor B associated with risk of chronic hepatitis B in a Korean population.

BMC Med Genet 2020 12 17;21(1):241. Epub 2020 Dec 17.

Department of Internal Medicine and Liver Research Institute, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Background: Hepatitis B is known to cause several forms of liver diseases including chronic hepatitis B (CHB), and hepatocellular carcinoma. Previous genome-wide association study of CHB risk has demonstrated that rs12614 of complement factor B (CFB) was significantly associated with CHB risk. In this study, fine-mapping study of previously reported GWAS single nucleotide polymorphism (SNP; CFB rs12614) was performed to validate genetic effect of rs12614 on CHB susceptibility and identify possible additional causal variants around rs12614 in a Korean population. This association study was conducted in order to identify genetic effects of CFB single nucleotide polymorphisms (SNPs) and to identify additional independent CHB susceptible causal markers within a Korean population.

Methods: A total of 10 CFB genetic polymorphisms were selected and genotyped in 1716 study subjects comprised of 955 CHB patients and 761 population controls.

Results: A non-synonymous variant, rs12614 (Arg32Trp) in exon2 of CFB, had significant associations with risk of CHB (odds ratio = 0.43, P = 5.91 × 10). Additional linkage disequilibrium and conditional analysis confirmed that rs12614 had independent genetic effect on CHB susceptibility with previously identified CHB markers. The genetic risk scores (GRSs) were calculated and the CHB patients had higher GRSs than the population controls. Moreover, OR was found to increase significantly with cumulative GRS.

Conclusions: rs12614 showed significant genetic effect on CHB risk within the Korean population. As such rs12614 may be used as a possible causal genetic variant for CHB susceptibility.
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http://dx.doi.org/10.1186/s12881-020-01177-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745368PMC
December 2020

The schizophrenia genetics knowledgebase: a comprehensive update of findings from candidate gene studies.

Transl Psychiatry 2019 08 27;9(1):205. Epub 2019 Aug 27.

Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia.

Over 3000 candidate gene association studies have been performed to elucidate the genetic underpinnings of schizophrenia. However, a comprehensive evaluation of these studies' findings has not been undertaken since the decommissioning of the schizophrenia gene (SzGene) database in 2011. As such, we systematically identified and carried out random-effects meta-analyses for all polymorphisms with four or more independent studies in schizophrenia along with a series of expanded meta-analyses incorporating published and unpublished genome-wide association (GWA) study data. Based on 550 meta-analyses, 11 SNPs in eight linkage disequilibrium (LD) independent loci showed Bonferroni-significant associations with schizophrenia. Expanded meta-analyses identified an additional 10 SNPs, for a total of 21 Bonferroni-significant SNPs in 14 LD-independent loci. Three of these loci (MTHFR, DAOA, ARVCF) had never been implicated by a schizophrenia GWA study. In sum, the present study has provided a comprehensive summary of the current schizophrenia genetics knowledgebase and has made available all the collected data as a resource for the research community.
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http://dx.doi.org/10.1038/s41398-019-0532-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711957PMC
August 2019

Epigenome-Wide Association Analysis of Differentially Methylated Signals in Blood Samples of Patients with Non-Small-Cell Lung Cancer.

J Clin Med 2019 Aug 25;8(9). Epub 2019 Aug 25.

Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.

Lung cancer is a common form of cancer and the leading cause of cancer-related deaths worldwide. Early diagnosis using noninvasive biomarkers may play an important role in increasing the survival rate of patients with lung cancer. Biomarkers of DNA methylation in blood samples may improve the early diagnosis of lung cancer. Here, we used peripheral blood samples obtained from 150 patients diagnosed with non-small-cell lung cancer (NSCLC) and 150 healthy controls. The latter were selected by frequency matching with the 150 patients with NSCLC, based on age, sex, and smoking status. Genome-wide methylation profiles were obtained using a MethylationEPIC BeadChip Kit, which covers the 850k bp cytosine-phosphate-guanine site. This analysis showed two significant differentially methylated changes (cg12169243 [] and cg25429010 []) associated with NSCLC in current smokers, six changes (cg09245319, cg17183999 [], cg06366994 [], cg24992236 [], cg22144719, and cg22448179 [epidermal growth factor receptor]) associated with epidermal growth factor receptor mutation in patients with adenocarcinoma, and four changes (cg25021476 [], cg04989085 [], cg20905681 [], and cg26379694) associated with advanced-stage NSCLC compared with stage I NSCLC. The validation of these DNA methylation changes and further research on the related genes may help develop easily accessible biomarkers for the early diagnosis or prognosis of NSCLC.
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http://dx.doi.org/10.3390/jcm8091307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780065PMC
August 2019

Global DNA Methylation Pattern of Fibroblasts in Idiopathic Pulmonary Fibrosis.

DNA Cell Biol 2019 Sep 15;38(9):905-914. Epub 2019 Jul 15.

Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea.

Our previous transcriptome study of cultured fibroblasts identified 178 genes that were differentially expressed by 8 idiopathic pulmonary fibrosis (IPF) fibroblasts compared with 4 controls. Here, we performed genome-wide DNA methylation analysis to evaluate the relationship of CpG methylation to differential gene expression. Among 485,577 loci, 5850 loci on 2282 genes showed significant differences between the 2 groups (delta-beta >10.21 and -value <0.05). Among these, beta values of 80 CpGs (30 hypermethylated and 50 hypomethylated) were significantly correlated with mRNA expression of 34 genes (19.1%) of the 178 differentially expressed genes between the 2 groups (13 downregulated and 21 upregulated). Gene ontology enrichment of these genes included cell adhesion, molecule binding, chemical homeostasis, surfactant homeostasis, and receptor binding. One-third of them are involved in the known process of fibrosis; the others are novel genes with respect to pulmonary fibrosis. We identified relationships between the altered DNA methylation levels and about one-fifth of the corresponding changes in gene expression by lung tissue fibroblasts. Findings from this study provide new information on novel genes responsible for the pathogenesis of IPF under the control of CpG methylation changes in IPF lungs.
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http://dx.doi.org/10.1089/dna.2018.4557DOI Listing
September 2019

A PHLDB1 variant associated with the nonfunctional pituitary adenoma.

J Neurooncol 2019 Apr 13;142(2):223-229. Epub 2019 Mar 13.

Department of Genetic Epidemiology, SNP Genetics Inc., Seoul, 04107, Republic of Korea.

Purpose: Previous studies have revealed that PHLDB1 single-nucleotide polymorphisms (SNPs) are associated with glioma risk. Nonetheless, the association between PHLDB1 SNPs and the risk of pituitary adenoma has not been studied. The present study evaluated the association of PHLDB1 SNPs with the risk of pituitary adenomas.

Methods: We genotyped 27 PHLDB1 tagging and exon SNPs in a case-control study that included 148 patients who got a diagnosis of nonfunctional pituitary adenoma (NFPA) and 375 normal controls within the Korean population. Statistical analyses of the association between PHLDB1 SNPs and the NFPA risk were conducted using logistic regression.

Results: We detected an association between a PHLDB1 SNP and the risk of NFPA in the Korean population. Rs67307131 in intron 2 was significantly associated with NFPA (odds ratio [OR] = 2.15, 95% confidence interval [CI] 1.44-3.20; P = 0.0002 in the dominant model). In the referent analysis, a higher OR and stronger association (lower P value) were observed among patients with the "C/T" genotype (OR = 2.39, 95% CI 1.60-3.58; P = 0.00002). In a functional analysis with a SNP annotation tool, this SNP was predicted to be a CpG site and copy number variant; these properties are associated with susceptibility to diseases.

Conclusions: Our findings suggest that genetic variation of PHLDB1 may be associated with the risk of NFPA. This is the first report of an association between PHLDB1 variants and NFPA. Further research is needed to confirm the impact of this SNP on NFPA susceptibility.
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http://dx.doi.org/10.1007/s11060-018-03082-yDOI Listing
April 2019

Associations between TMEM196 polymorphisms and NSAID-exacerbated respiratory disease in asthma.

Pharmacogenet Genomics 2019 06;29(4):69-75

Department of Medical Bioscience, Graduate School, Soonchunhyang University, Asan.

Background: We previously found differences in the minor allele frequency (MAF) of single-nucleotide polymorphisms (SNPs) in transmembrane protein 196 (TMEM196) between 995 patients with aspirin-tolerant asthma (ATA) and 141 asthmatic patients with NSAID-exacerbated respiratory disease (NERD). In this study, we statistically analyzed the distributions of the genotypes and haplotypes of these SNPs to determine the exact association between TMEM196 genetic variants and the risk for NERD.

Materials And Methods: Lewontin's D' and r values were used to measure linkage disequilibrium between the biallelic loci having MAFs more than 0.05, and haplotypes were inferred using the PHASE algorithm (version 2.0). The genotype distribution was analyzed by logistic regression models using age of onset, smoking status (nonsmoker=0, ex-smoker=1, smoker=2), and BMI as covariates. Regression analysis of the association between SNPs and the risk of NERD was analyzed using SPSS version 12.0 and PLINK version 1.9.

Results: The MAF of rs9886152 C>T was significantly lower in NERD than in ATA [24.8 vs. 34.0%, odds ratio=0.64 (0.48-0.85), P=2.07×10, Pcorr=0.048]. The rate of the rs9886152 C>T minor allele was significantly lower in NERD than in ATA [44.0 vs. 56.4% in the codominant model, P=0.002, Pcorr=0.049, odds ratio=0.64 (0.48-0.85)]. An additional three SNPs (rs9639334 A>G, rs9638765 A>G, and rs2097811 G>A) showed similar associations with the risk of NERD. NERD patients had lower frequencies of the rs9639334 A>G minor allele (51.1 vs. 64.4%, P=0.002, Pcorr=0.043), rs9638765 A>G (49.7 vs. 64.2%, P=0.001, Pcorr=0.017), and rs2097811 G>A (51.1 vs. 64.5%, P=0.002, Pcorr=0.04) compared with ATA patients. Patients homozygous for the minor alleles of the four SNPs showed significantly less of an aspirin-induced decrease in forced expiratory volume in one second compared with those homozygous for the common alleles (P=0.003-0.012).

Conclusion: The minor alleles of the four SNPs in TMEM196 may exert a protective effect against the development of NERD and may be useful genetic markers to predict the risk of NERD.
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http://dx.doi.org/10.1097/FPC.0000000000000367DOI Listing
June 2019

Association analysis of NOX5 polymorphisms with Hirschsprung disease.

J Pediatr Surg 2019 Sep 3;54(9):1815-1819. Epub 2019 Jan 3.

Department of Life Science, Sogang University, Seoul 04107, Republic of Korea; Research Institute for Basic Science, Sogang University, Seoul 04107, Republic of Korea. Electronic address:

Background/purpose: Hirschsprung disease (HSCR) is a developmental disease characterized by the absence of ganglion cells in the intestinal region. NADPH oxidase5 (NOX5) has been identified as one of the possible candidate genes for risk of Hirschsprung disease in our recent genome wide association study (GWAS). In this study, we performed a replication study to analyze the association of NOX5 polymorphisms with HSCR risk and conducted an extended analysis to investigate further associations for sub-groups and haplotypes.

Methods: A total of 23 NOX5 single nucleotide polymorphisms (SNPs) were genotyped in 187 HSCR patients and 283 unaffected controls. Statistical analysis was performed to examine the effects of genotype on risk of HSCR and HSCR subtype.

Results: Logistic regression analyses revealed that six SNPs (rs59355559, rs62010828, rs34990910, rs11856030, rs311905, and rs8024894) were associated with risk of HSCR (minimum p = 0.007 at rs62010828). Moreover, three SNPs (rs59355559, rs62010828, and rs8024894) were significantly associated with risk of long-segment HSCR (L-HSCR) subtype and 5 SNPs (rs59355559, rs62010828, rs34990910, rs11856030, and rs8024894) were found to be associated with risk of TCA subtype.

Conclusion: Our results demonstrate that genetic variants in NOX5 have genetic effects on risk of HSCR, which may serve as useful preliminary information for further study.

Levels Of Evidence: Level III of prognosis study.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.12.017DOI Listing
September 2019

Association of Genetic Variants of NLRP4 with Exacerbation of Asthma: The Effect of Smoking.

DNA Cell Biol 2019 Jan 8;38(1):76-84. Epub 2018 Dec 8.

5 Department of Interdisciplinary Program in Biomedical Science Major, Graduate School, Soonchunhyang University , Bucheon, Korea.

Asthma exacerbation is induced by the interaction of genes and environmental factors such as cigarette smoke. NLRP4 counteracts the activity of the inflammasome, which is responsible for asthma exacerbation. In this study, we analyzed the association of single-nucleotide polymorphisms of NLRP4 with the annual rate of exacerbation and evaluated the additive effect of smoking in 1454 asthmatics. Asthmatics possessing the minor allele of rs1696718G > A had more frequent exacerbation episodes than those homozygous for the common allele (0.59 vs. 0.36/year) and the association was present only in current and ex-smokers. There was a significant interaction between the amount smoked and rs16986718 genotypes (p = 0.014) and a positive correlation between the number of annual exacerbation episodes and amount smoked only in rs16986718G > A AA homozygotes. The prevalence of frequent exacerbators (≥2 exacerbation episodes/year) was 2.5 times higher in rs16986718G > A minor allele homozygotes than in common allele homozygotes (12.0% vs. 5.9%). Furthermore, the prevalence was 6 times higher in rs16986718G > A minor allele homozygotes who were current and ex-smokers than in nonsmokers (25.6% vs. 4.1%). The minor allele of rs16986718G > A in NLRP4 may be a genetic marker that predicts asthma exacerbation in adult asthmatics who smoke.
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http://dx.doi.org/10.1089/dna.2018.4433DOI Listing
January 2019

Association analysis of RTEL1 variants with risk of adult gliomas in a Korean population.

PLoS One 2018 21;13(11):e0207660. Epub 2018 Nov 21.

Department of Life Science, Sogang University, Seoul, Republic of Korea.

Previous studies have identified multiple loci for inherited susceptibility to glioma development, including the regulator of telomere elongation helicase 1 (RTEL1). However, the association between RTEL1 variants and risk of glioma has not been well understood. Therefore, we sought to comprehensively examine the genetic interaction between RTEL1 variants and risk of glioma with respect to defined histological and molecular subtypes. We employed a case-control study involving 250 adult glioma patients with previous molecular alterations and 375 population-based controls within Korean populations. Statistical analyses on the association between RTEL1 single nucleotide polymorphisms (SNPs) and glioma risk were conducted using unconditional logistic regression. Additional conditional and stepwise analyses were performed on significant RTEL1 SNPs. We detected significant associations (Bonferroni P < .05) between six SNPs (rs6089953, rs3848669, rs6010620, rs3787089, rs6062302, and rs115303435) and risk of glioma in the Korean subjects. The two coding variants, rs6062302 (D664D) and rs115303435 (A1059T), were plausibly causal variants and were independent among the significantly associated RTEL1 variants. The glioma subgroup analyses showed that the causal variants (rs6062302 and rs115303435) may be associated with increased risk of glioma regardless of histological grades and molecular alterations. This study provides a deeper understanding of relationships between RTEL1 variants and risk of glioma. Further studies are required to ascertain the impact of those variants on glioma susceptibility.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207660PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248978PMC
April 2019

Selective Elimination of Culture-Adapted Human Embryonic Stem Cells with BH3 Mimetics.

Stem Cell Reports 2018 11 4;11(5):1244-1256. Epub 2018 Oct 4.

School of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea. Electronic address:

The selective survival advantage of culture-adapted human embryonic stem cells (hESCs) is a serious safety concern for their clinical application. With a set of hESCs with various passage numbers, we observed that a subpopulation of hESCs at late passage numbers was highly resistant to various cell death stimuli, such as YM155, a survivin inhibitor. Transcriptome analysis from YM155-sensitive (YM155S) and YM155-resistant (YM155R) hESCs demonstrated that BCL2L1 was highly expressed in YM155R hESCs. By matching the gene signature of YM155R hESCs with the Cancer Therapeutics Response Portal dataset, BH3 mimetics were predicted to selectively ablate these cells. Indeed, short-course treatment with a sub-optimal dose of BH3 mimetics induced the spontaneous death of YM155R, but not YM155S hESCs by disrupting the mitochondrial membrane potential. YM155S hESCs remained pluripotent following BH3 mimetics treatment. Therefore, the use of BH3 mimetics is a promising strategy to specifically eliminate hESCs with a selective survival advantage.
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http://dx.doi.org/10.1016/j.stemcr.2018.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235677PMC
November 2018

Genetic diversity and divergence among Korean cattle breeds assessed using a BovineHD single-nucleotide polymorphism chip.

Asian-Australas J Anim Sci 2018 Nov 26;31(11):1691-1699. Epub 2018 Jul 26.

Animal Genetic Resources Center, National Institute of Animal Science, RDA, Namwon 55717, Korea.

Objective: In Korea, there are three main cattle breeds, which are distinguished by coat color: Brown Hanwoo (BH), Brindle Hanwoo (BRH), and Jeju Black (JB). In this study, we sought to compare the genetic diversity and divergence among there Korean cattle breeds using a BovineHD chip genotyping array.

Methods: Sample data were collected from 168 cattle in three populations of BH (48 cattle), BRH (96 cattle), and JB (24 cattle). The single-nucleotide polymorphism (SNP) genotyping was performed using the Illumina BovineHD SNP 777K Bead chip.

Results: Heterozygosity, used as a measure of within-breed genetic diversity, was higher in BH (0.293) and BRH (0.296) than in JB (0.266). Linkage disequilibrium decay was more rapid in BH and BRH than in JB, reaching an average r² value of 0.2 before 26 kb in BH and BRH, whereas the corresponding value was reached before 32 kb in JB. Intra-population, inter-population, and Fst analyses were used to identify candidate signatures of positive selection in the genome of a domestic Korean cattle population and 48, 11, and 11 loci were detected in the genomic region of the BRH breed, respectively. A Neighbor-Joining phylogenetic tree showed two main groups: a group comprising BH and BRH on one side and a group containing JB on the other. The runs of homozygosity analysis between Korean breeds indicated that the BRH and JB breeds have high inbreeding within breeds compared with BH. An analysis of differentiation based on a high-density SNP chip showed differences between Korean cattle breeds and the closeness of breeds corresponding to the geographic regions where they are evolving.

Conclusion: Our results indicate that although the Korean cattle breeds have common features, they also show reliable breed diversity.
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http://dx.doi.org/10.5713/ajas.17.0419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212751PMC
November 2018

Prediction of cholesterol ratios within a Korean population.

R Soc Open Sci 2018 Jan 17;5(1):171204. Epub 2018 Jan 17.

Department of Life Science, Sogang University, Baekbumro 35, Mapo-gu, Seoul 04107, Republic of Korea.

Cholesterol ratios (total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-c) and triglyceride (TG)/HDL-c) have been suggested as better indicators to predict various clinical features such as insulin resistance and heart disease. Therefore, we aimed to build a single nucleotide polymorphism (SNP) set to predict constitutional lipid metabolism. The genotype data of 7795 samples were obtained from the Korea Association Resource. Among the total of 7795 samples, 7016 subjects were used to perform 10-fold cross-validation. We selected the SNPs that showed significance constantly throughout all 10 cross-validation sets; another 779 samples were used as the final validation set. After performing the 10-fold cross-validation, the six SNPs ( (), () () () () and ()) were finally selected for predicting cholesterol ratios. The weighted genetic risk scores (wGRS) were calculated based on the regression slopes of the six selected SNPs. Our results showed upward trends of wGRS for both the TC/HDL-c and TG/HDL-c ratios within the 10-fold cross-validation. Similarly, the wGRS of the six SNPs also showed upward trends in analyses using the SNP selection set and final validation set. The selected six SNPs can be used to explain both the TC/HDL-c and TG/HDL-c ratios. Our results may be useful for the prospective predictions of cholesterol-related diseases.
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http://dx.doi.org/10.1098/rsos.171204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5792909PMC
January 2018

Genetic association of complement component 2 variants with chronic hepatitis B in a Korean population.

Liver Int 2018 09 10;38(9):1576-1582. Epub 2018 Feb 10.

Department of Internal Medicine and Liver Research Institute, Seoul National University, Seoul, Korea.

Background & Aims: Numerous single nucleotide polymorphisms associated with an increased risk of liver diseases, chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma have been identified. In this study, we scrutinized the genetic effects of C2 variants, which were conflicting in previous results, on the risk of chronic hepatitis B in a Korean population.

Methods: We genotyped 22 common C2 genetic variants of 977 chronic hepatitis B cases including 302 chronic hepatitis B-related hepatocellular carcinoma cases and 785 population controls. Statistical analysis was performed to examine the effects of genotype on the risk of chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma.

Results: Logistic regression analyses showed that six C2 single nucleotide polymorphisms had significant associations with the risk of chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma among the Korean subjects. Stepwise analysis revealed that causal markers (rs9267665 and rs10947223) were identified among the C2 variants (stepwise P = 3.32 × 10 and 2.04 × 10 respectively). In further conditional analysis with previous chronic hepatitis B-associated loci, these two single nucleotide polymorphisms were independently associated with the risk of chronic hepatitis B. In addition, we investigated the ability of genetic risk scores combining 12 multi-chronic hepatitis B loci to predict the risk of chronic hepatitis B. Individuals with higher genetic risk scores showed increased risk for chronic hepatitis B.

Conclusions: Our results suggested that the C2 gene might be a susceptibility locus for chronic hepatitis B in Korean populations. The cumulative genetic effects may contribute to future etiological explanations for chronic hepatitis B.
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http://dx.doi.org/10.1111/liv.13675DOI Listing
September 2018

Association analysis of ILVBL gene polymorphisms with aspirin-exacerbated respiratory disease in asthma.

BMC Pulm Med 2017 Dec 16;17(1):210. Epub 2017 Dec 16.

Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung-Dong, Wonmi-Ku, Bucheon, Gyeonggi-Do, 420-021, Republic of Korea.

Background: We previously reported that the ILVBL gene on chromosome 19p13.1 was associated with the risk for aspirin-exacerbated respiratory disease (AERD) and the percent decline of forced expired volume in one second (FEV1) after an oral aspirin challenge test. In this study, we confirmed the association between polymorphisms and haplotypes of the ILVBL gene and the risk for AERD and its phenotype.

Methods: We recruited 141 AERD and 995 aspirin-tolerant asthmatic (ATA) subjects. All study subjects underwent an oral aspirin challenge (OAC). Nine single nucleotide polymorphisms (SNPs) with minor allele frequencies above 0.05, which were present in the region from 2 kb upstream to 0.5 kb downstream of ILVBL in Asian populations, were selected and genotyped.

Results: In an allelic association analysis, seven of nine SNPs were significantly associated with the risk for AERD after correction for multiple comparisons. In a codominant model, the five SNPs making up block2 (rs2240299, rs7507755, rs1468198, rs2074261, and rs13301) showed significant associations with the risk for AERD (corrected P = 0.001-0.004, OR = 0.59-0.64). Rs1468198 was also significantly associated with the percent decline in FEV1 in OAC tests after correction for multiple comparisons in the codominant model (corrected P = 0.033), but the other four SNPs in hapblock2 were not.

Conclusion: To the best of our knowledge, this is the first report of an association between SNPs on ILVBL and AERD. SNPs on ILVBL could be promising genetic markers of this condition.
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http://dx.doi.org/10.1186/s12890-017-0556-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732499PMC
December 2017

Identification of additional EHMT2 variant associated with the risk of chronic hepatitis B by GWAS follow-up study.

Genes Immun 2019 01 14;20(1):1-9. Epub 2017 Dec 14.

Department of Life Science, Sogang University, 1 Shinsu-dong, Mapo-gu, Seoul, 121-742, Republic of Korea.

Chronic hepatitis B (CHB) is a precursor to liver cirrhosis and hepatocellular carcinoma, caused by a Hepatitis B viral infection. Genome-wide association studies (GWASs) have been conducted to find genes associated with CHB risk. In previous GWAS, EHMT2 was identified as one of the susceptibility genes for CHB. To further characterize this association and discover possible causal variants, we conducted an additional association study. A total of 11 EHMT2 single-nucleotide polymorphisms (SNP) were selected and genotyped in 3902 subjects (1046 CHB patients and 2856 controls). An additional eight imputed SNPs were also included in further analysis. As a result, rs35875104 showed a strong association with the CHB, along with the previously reported genetic marker for CHB risk, rs652888 (odds ratio (OR) = 0.53, P = 2.20 × 10 at rs35875104 and OR = 1.58, P = 9.90 × 10 at rs652888). In addition, linkage disequilibrium and conditional analysis identified one SNP (rs35875104) as a novel genetic marker for CHB susceptibility. The GRSs (genetic risk scores) were calculated to visualize the combined genetic effects of all known CHB-associated loci, including EHMT2 rs35875104, which was additionally identified in this study. The findings from the present study may be useful for further understanding of the genetic etiology of CHB.
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http://dx.doi.org/10.1038/s41435-017-0004-xDOI Listing
January 2019

BMI prediction within a Korean population.

PeerJ 2017 29;5:e3510. Epub 2017 Jun 29.

Research Institute for Basic Science, Sogang University, Seoul, Republic of Korea.

Background: Body Mass Index (BMI) is widely regarded as an important clinical trait for obesity and other diseases such as Type 2 diabetes, coronary heart disease, and osteoarthritis.

Methods: This study uses 6,011 samples of genotype data from ethnic Korean subjects. The data was retrieved from the Korea Association Resource. To identify the BMI-related markers within the Korean population, we collected genome-wide association study (GWAS) markers using a GWAS catalog and also obtained other markers from nearby regions. Of the total 6,011 samples, 5,410 subjects were used as part of a single nucleotide polymorphism (SNP) selection set in order to identify the overlapping BMI-associated SNPs within a 10-fold cross validation.

Results: We selected nine SNPs ( (), (), (located near ), (located near ), (), (), (), (), and (located near ) to assist in BMI prediction. The calculated weighted genetic risk scores based on the selected 9 SNPs within the SNP selection set were applied to the final validation set consisting of 601 samples. Our results showed upward trends in the BMI values ( < 0.0001) within the 10-fold cross validation process for  > 0.22. These trends were also observed within the validation set for all subjects, as well as within the validation sets divided by gender ( < 0.0001,  > 0.46).

Discussion: The set of nine SNPs identified in this study may be useful for prospective predictions of BMI.
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http://dx.doi.org/10.7717/peerj.3510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493974PMC
June 2017

Potential association between ITPKC genetic variations and Hirschsprung disease.

Mol Biol Rep 2017 Jul 29;44(3):307-313. Epub 2017 Jun 29.

Research Institute for Basic Science, Sogang University, Seoul, 04107, Republic of Korea.

Hirschsprung disease (HSCR) is a congenital and complex disorder characterized by intestinal obstruction due to the absence of enteric neurons along variable lengths of the hindgut. Our recent genome-wide association study (GWAS) has revealed regional associations with HSCR at several loci of inositol-trisphosphate 3-kinase C (ITPKC). For fine mapping, we additionally selected and genotyped a total of 12 single nucleotide polymorphisms (SNPs) of ITPKC in 187 HSCR patients and 283 unaffected controls, and performed a further combined imputation analysis based on genotype data from this second stage of fine mapping and our previous GWAS stage, totaling 902 subjects (187 HSCR cases and 715 controls). As a result, several SNPs (minimum P = 0.004) and a haplotype (P = 0.02) were found to be significantly associated with HSCR. In further in silico analyses to ascertain the potential functions of the significant variants, the change from the common allele to the rare allele of the highly conserved nonsynonymous rs76785336 showed a difference in mRNA folding structure. In the case of intronic SNPs, rs2607420 with a high consensus value was predicted to be a new splice site. Although this study has limitations (such as lack of functional evaluations, small number of cases, and further need of replication in other cohorts), our findings suggest that genetic variants of ITPKC may have a potential association with HSCR susceptibility and/or developmental diseases related to enteric nervous system development.
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http://dx.doi.org/10.1007/s11033-017-4111-6DOI Listing
July 2017

PRMT8 Controls the Pluripotency and Mesodermal Fate of Human Embryonic Stem Cells By Enhancing the PI3K/AKT/SOX2 Axis.

Stem Cells 2017 09 31;35(9):2037-2049. Epub 2017 May 31.

Department of Life Sciences, Sogang University, Seoul, Republic of Korea.

Basic fibroblast growth factor (bFGF) supplementation is critical to maintain the pluripotency of human pluripotent stem cells (hPSCs) through activation of PI3K/AKT, rather than MEK/ERK pathway. Thus, elaborate molecular mechanisms that preserve PI3K/AKT signaling upon bFGF stimulation may exist in hPSCs. Protein arginine methyltransferase 8 (PRMT8) was expressed and then its level gradually decreased during spontaneous differentiation of human embryonic stem cells (hESCs). PRMT8 loss- or gain-of-function studies demonstrated that PRMT8 contributed to longer maintenance of hESC pluripotency, even under bFGF-deprived conditions. Direct interaction of membrane-localized PRMT8 with p85, a regulatory subunit of PI3K, was associated with accumulation of phosphoinositol 3-phosphate and consequently high AKT activity. Furthermore, the SOX2 induction, which was controlled by the PRMT8/PI3K/AKT axis, was linked to mesodermal lineage differentiation. Thus, we propose that PRMT8 in hESCs plays an important role not only in maintaining pluripotency but also in controlling mesodermal differentiation through bFGF signaling toward the PI3K/AKT/SOX2 axis. Stem Cells 2017;35:2037-2049.
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http://dx.doi.org/10.1002/stem.2642DOI Listing
September 2017

Undifferentiated embryonal sarcoma of the liver in a child: A whole exome sequencing analysis.

Dig Liver Dis 2017 Aug 3;49(8):944-946. Epub 2017 May 3.

Department of Surgery, Jeju National University Hospital, Jeju 63241, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.dld.2017.04.020DOI Listing
August 2017

Comparison of commonly used ICR stocks and the characterization of Korl:ICR.

Lab Anim Res 2017 Mar 27;33(1):8-14. Epub 2017 Mar 27.

Laboratory Animal Resources Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Cheongju, Korea.

Mouse is a commonly used animal in life science studies and is classified as outbred if genetically diverse and inbred if genetically homogeneous. Outbred mouse stocks, are used in toxicology, oncology, infection and pharmacology research. The National Institute of Food and Drug Safety Evaluation (NIFDS; former the Korea National Institute of Health) have bred ICR mice for more than 50 years. We investigated to provide users with information and promote accountability to the Korl:ICR. To secure the indigenous data, biological characteristics of Korl:ICR were identified by comparing with other ICR stocks. This domestic ICR stock was denominated as 'Korl:ICR'. Phylogenetic analysis using SNPs indicated that the population stratification of the Korl:ICR was allocated different area with other ICR. In addition, we measured litter size, body weight, body length, various organ weight, hematology and clinical blood chemistry of the Korl:ICR compared to other ICR. Otherwise, there are no significant differences among the biological phenotypes of Korl:ICR and other ICR. These results suggest that as a genetically indigenous source colony, the Korl:ICR is seperated (or independent) stock with other ICR. Also, we confirmed that there is no difference among the Korl:ICR and other ICR on biological phenotypes. Therefore, the Korl:ICR source colony might be a new stock in distinction from other ICR, it is a good milestone in securing ownership of the national laboratory animal resource. The NIFDS expects that the Korl:ICR mice will be useful animal resource for our domestic researchers.
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http://dx.doi.org/10.5625/lar.2017.33.1.8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385282PMC
March 2017

Sotos syndrome associated with Hirschsprung's disease: a new case and exome-sequencing analysis.

Pediatr Res 2017 07 3;82(1):87-92. Epub 2017 May 3.

Research Institute for Basic Science, Sogang University, Seoul, Republic of Korea.

BackgroundSotos syndrome (SoS) is an overgrowth disorder with various congenital anomalies and is usually accompanied by other clinical problems. However, anorectal malformations have not been documented as part of the SoS entity. Our objective is to report on a case of SoS associated with Hirschsprung's disease (HSCR) and subsequent genetic analysis.MethodsA 2-year-old boy with SoS experienced constipation since infancy and ultimately showed an aganglionic segment in the histopathologic examination, which was followed by exome-sequencing analysis.ResultsIn the genetic test for SoS diagnosis, two novel mutations of NDS1, c.2465C>A (p.Ser822Tyr) and c.4347T>A (p.Cys1449*), were observed and verified by resequencing in the patient and his parents. In further whole-exome-sequencing analysis using the patient's blood DNA, which was followed by a comparison analysis with the results of our previously reported genome-wide association study (GWAS) of HSCR, three genes (ZNF827, FGD2, and KCNJ12) with significance for HSCR from our previous GWAS were overlapped among the genes showing variants in the exome sequencing.ConclusionThis is the first reported patient with SoS and HSCR. Further studies are required to determine whether there is a genetic relationship between SoS and HSCR.
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http://dx.doi.org/10.1038/pr.2017.106DOI Listing
July 2017

RNA-Seq for Gene Expression Profiling of Human Necrotizing Enterocolitis: a Pilot Study.

J Korean Med Sci 2017 May;32(5):817-824

Research Institute for Basic Science, Sogang University, Seoul, Korea.

Necrotizing enterocolitis (NEC) characterized by inflammatory intestinal necrosis is a major cause of mortality and morbidity in newborns. Deep RNA sequencing (RNA-Seq) has recently emerged as a powerful technology enabling better quantification of gene expression than microarrays with a lower background signal. A total of 10 transcriptomes from 5 pairs of NEC lesions and adjacent normal tissues obtained from preterm infants with NEC were analyzed. As a result, a total of 65 genes (57 down-regulated and 8 up-regulated) revealed significantly different expression levels in the NEC lesion compared to the adjacent normal region, based on a significance at fold change ≥ 1.5 and P ≤ 0.05. The most significant gene, DPF3 (P < 0.001), has recently been reported to have differential expressions in colon segments. Our gene ontology analysis between NEC lesion and adjacent normal tissues showed that down-regulated genes were included in nervous system development with the most significance (P = 9.3 × 10⁻⁷; P(corr) = 0.0003). In further pathway analysis using Pathway Express based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, genes involved in thyroid cancer and axon guidance were predicted to be associated with different expression (P(corr) = 0.008 and 0.020, respectively). Although further replications using a larger sample size and functional evaluations are needed, our results suggest that altered gene expression and the genes' involved functional pathways and categories may provide insight into NEC development and aid in future research.
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http://dx.doi.org/10.3346/jkms.2017.32.5.817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383615PMC
May 2017

X Chromosome-wide Association Study Identifies a Susceptibility Locus for Inflammatory Bowel Disease in Koreans.

J Crohns Colitis 2017 Jul;11(7):820-830

Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.

Background And Aims: Genome-wide association studies of inflammatory bowel disease identified > 200 susceptibility loci only in autosomes. This study aimed to identify inflammatory bowel disease susceptibility loci on the X chromosome.

Methods: We performed an X chromosome-wide association study in Korean patients with inflammatory bowel disease. We analysed X chromosome data from our recent genome-wide association studies, including 1505 cases [922 Crohn's disease and 583 ulcerative colitis] and 4041 controls during the discovery phase, followed by replication in additional 1989 cases [993 Crohn's disease, 996 ulcerative colitis] and 3491 controls. Sex-related differential effects of single nucleotide polymorphisms on disease were also evaluated.

Results: We confirmed a significant association of a previously reported inflammatory bowel disease susceptibility locus at chromosome Xq26.3 [CD40LG-ARHGEF6; odds ratio, 1.22; 95% confidence interval, 1.16-1.28; combined p = 3.79 × 10-15]. This locus accounted for 0.18% and 0.12% of genetic variance in Crohn's disease and ulcerative colitis, respectively, and increased the total autosomal chromosome genetic variance from 6.65% to 6.83% and from 5.47% to 5.59% for Crohn's disease and ulcerative colitis risk, respectively, in the Korean population. Sex-stratified analyses did not reveal sex-related differences in effect sizes.

Conclusions: We confirmed the association of rs2427870 at the CD40LG-ARHGEF6 locus with an inflammatory bowel disease through an X chromosome-wide association study in a Korean population. Our data suggest that the CD40LG-ARHGEF6 locus on the X chromosome might play a role in inflammatory bowel disease pathogenesis in the Korean population.
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http://dx.doi.org/10.1093/ecco-jcc/jjx023DOI Listing
July 2017

Gender-Specific Associations between CHGB Genetic Variants and Schizophrenia in a Korean Population.

Yonsei Med J 2017 May;58(3):619-625

Department of Neuropsychiatry, Soonchunhyang University Hospital, Seoul, Korea.

Purpose: Schizophrenia is a devastating mental disorder and is known to be affected by genetic factors. The chromogranin B (CHGB), a member of the chromogranin gene family, has been proposed as a candidate gene associated with the risk of schizophrenia. The secretory pathway for peptide hormones and neuropeptides in the brain is regulated by chromogranin proteins. The aim of this study was to investigate the potential associations between genetic variants of CHGB and schizophrenia susceptibility.

Materials And Methods: In the current study, 15 single nucleotide polymorphisms of CHGB were genotyped in 310 schizophrenia patients and 604 healthy controls.

Results: Statistical analysis revealed that two genetic variants (non-synonymous rs910122; rs2821 in 3'-untranslated region) were associated with schizophrenia [minimum p=0.002; odds ratio (OR)=0.72], even after correction for multiple testing (p(corr)=0.02). Since schizophrenia is known to be differentially expressed between sexes, additional analysis for sex was performed. As a result, these two genetic variants (rs910122 and rs2821) and a haplotype (ht3) showed significant associations with schizophrenia in male subjects (p(corr)=0.02; OR=0.64), whereas the significance disappeared in female subjects (p>0.05).

Conclusion: Although this study has limitations including a small number of samples and lack of functional study, our results suggest that genetic variants of CHGB may have sex-specific effects on the risk of schizophrenia and provide useful preliminary information for further study.
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http://dx.doi.org/10.3349/ymj.2017.58.3.619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368149PMC
May 2017

Gene profile of fibroblasts identify relation of CCL8 with idiopathic pulmonary fibrosis.

Respir Res 2017 01 5;18(1). Epub 2017 Jan 5.

Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School, Bucheon, Korea.

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by the complex interaction of cells involved in chronic inflammation and fibrosis. Global gene expression of a homogenous cell population will identify novel candidate genes.

Methods: Gene expression of fibroblasts derived from lung tissues (8 IPF and 4 controls) was profiled, and ontology and functional pathway were analyzed in the genes exhibiting >2 absolute fold changes with p-values < 0.05. CCL8 mRNA and protein levels were quantified using real-time PCR and ELISA. CCL8 localization was evaluated by immunofluorescence staining.

Results: One hundred seventy eight genes differentially expressed and 15 genes exhibited >10-fold change. Among them, 13 were novel in relation with IPF. CCL8 expression was 22.8-fold higher in IPF fibroblasts. The levels of CCL8 mRNA and protein were 3 and 9-fold higher in 14 IPF fibroblasts than those in 10 control fibroblasts by real-time PCR and ELISA (p = 0.022 and p = 0.026, respectively). The CCL8 concentrations in BAL fluid was significantly higher in 86 patients with IPF than those in 41 controls, and other interstitial lung diseases including non-specific interstitial pneumonia (n = 22), hypersensitivity pneumonitis (n = 20) and sarcoidosis (n = 19) (p < 0.005, respectively). Cut-off values of 2.29 pg/mL and 0.43 pg/mL possessed 80.2 and 70.7% accuracy for the discrimination of IPF from NC and the other lung diseases, respectively. IPF subjects with CCL8 levels >28.61 pg/mL showed shorter survival compared to those with lower levels (p = 0.012). CCL8 was expressed by α-SMA-positive cells in the interstitium of IPF.

Conclusions: Transcriptome analysis identified several novel IPF-related genes. Among them, CCL8 is a candidate molecule for the differential diagnosis and prediction of survival.
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http://dx.doi.org/10.1186/s12931-016-0493-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216573PMC
January 2017

Genetic variants of the gasdermin B gene associated with the development of aspirin-exacerbated respiratory diseases.

Allergy Asthma Proc 2017 Jan;38(1):4-12

Background: Aspirin-exacerbated respiratory disease (AERD) is characterized by a severe and sudden asthma attack after aspirin ingestion in patients with asthma. We studied associations with six common single nucleotide polymorphisms (SNP) of the gasdermin B gene (GSDMB).

Objective: DNA obtained from 572 patients with asthma (with AERD, n = 165; and with aspirin-tolerant asthma, n = 407) and 391 normal controls was subjected to genotyping of six SNPs of GSDMB.

Methods: An association analysis between GSDMB variants and AERD, with a fall rate of the forced expiratory volume in the first second of expiration (FEV1), was performed by using logistic and regression models.

Results: Two SNPs in the intron (rs870830, rs7216389) showed significant associations with AERD (minimum p = 7.00 × 10-4 in the dominant model), even after Bonferroni correction (pcorr = 0.01 for the rs870830). Regression analysis of the genetic variants with FEV1 revealed significant associations with rs870830 and the haplotype 2 (pcorr = 4.71 × 10-4 for rs870830 and pcorr = 1.14 × 10-3 for haplotype 2, respectively).

Conclusion: We found strong associations among GSDMB polymorphisms and the presence of AERD and FEV1 in Korean patients with asthma. Our findings indicated that genetic variations of GSDMB may be associated with the development of AERD and aspirin-induced bronchospasm.
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http://dx.doi.org/10.2500/aap.2017.38.4014DOI Listing
January 2017

Expression efficiency of NAT2 haplotypes in a Korean population.

Genes Genet Syst 2017 Apr 15;91(5):277-281. Epub 2016 Nov 15.

Clinical Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex.

Since NAT2 single-nucleotide polymorphisms (SNPs) are responsible for the efficacy of arylamines and hydrazine drugs, defining the effects of these SNPs in various ethnicities is an important factor in the development of personalized medicine. In the present study, we examined the expression efficiency of NAT2 using promoter haplotypes identified in a Korean population. To construct NAT2 promoter haplotypes, seven NAT2 promoter SNPs (rs4646241, rs4646242, rs4646243, rs4646267, rs4345600, rs4271002 and rs4646246) were genotyped in a total of 192 Korean subjects. A luciferase assay was performed using the three commonest haplotypes to evaluate enzyme expression level of NAT2 promoter haplotypes. The most common haplotype (TACGAGG) showed the lowest enzyme expression level (0.72 ± 0.06 relative light units (RLU)/[β-galactosidase]). The second (CGTAAGA) and third (TATAACA) commonest haplotypes showed intermediate and the highest enzyme expression level (0.99 ± 0.05 and 1.45 ± 0.11 RLU/[β-galactosidase]), respectively. Haplotype comparison among populations showed that Asian populations had a high proportion of the haplotype for lowest enzyme expression. Haplotype frequencies of Caucasian and African ethnicities were markedly different from those of Korean ethnicity. Results from the present study should contribute to the expansion of our current understanding of the pharmacogenetics field.
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http://dx.doi.org/10.1266/ggs.15-00081DOI Listing
April 2017

MCM7 polymorphisms associated with the AML relapse and overall survival.

Ann Hematol 2017 Jan 12;96(1):93-98. Epub 2016 Nov 12.

Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

The minichromosome maintenance complex component 7 (MCM7) encodes a member of MCM complex, which plays a critical role in the initiation of gene replication. Due to the importance of MCM complex, MCM7 gene has been regarded as a candidate gene for cancer development. In the present study, seven MCM7 polymorphisms were genotyped in 344 subjects composed of 103 acute myeloid leukemia (AML) patients and 241 normal controls to examine the possible associations between MCM7 polymorphisms and the risk of AML. MCM7 polymorphisms were not associated with the risk of AML (P > 0.05). However, MCM7 polymorphisms were significantly related to the relapse of AML and overall survival. The rs2070215 (N144S) showed a protective effect to the risk of AML relapse (OR = 0.37; P  = 0.02). In haplotype analyses, the ht1 and ht2 showed significant associations with the risk of AML relapse (P  = 0.02-0.03). In addition, rs1534309 showed an association with the overall survival of AML patients. Patients with major homozygote genotype (CC) of rs1534309 showed a higher survival rate than the patients with other genotypes (CG and GG). The results of the present study indicate that MCM7 polymorphisms may be able to predict the prognosis of AML patients.
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http://dx.doi.org/10.1007/s00277-016-2844-2DOI Listing
January 2017

Identification of Loci at 1q21 and 16q23 That Affect Susceptibility to Inflammatory Bowel Disease in Koreans.

Gastroenterology 2016 Dec 26;151(6):1096-1099.e4. Epub 2016 Aug 26.

Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea. Electronic address:

Recent genome-wide association studies have identified more than 200 regions that affect susceptibility to inflammatory bowel disease (IBD). However, identified common variants account for only a fraction of IBD heritability and largely have been identified in populations of European ancestry. We performed a genome-wide association study of susceptibility loci in Korean individuals, comprising a total of 1505 IBD patients and 4041 controls. We identified 2 new susceptibility loci for IBD at genome-wide significance: rs3766920 near PYGO2-SHC1 at 1q21 and rs16953946 in CDYL2 at 16q23. In addition, we confirmed associations, in Koreans, with 28 established IBD loci (P < 2.16 × 10). Our findings support the complementary value of genetic studies in different populations.
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http://dx.doi.org/10.1053/j.gastro.2016.08.025DOI Listing
December 2016